Known Benefits and Unknown Risks of Active Surveillance of Cervical Intraepithelial Neoplasia Grade 2

Abstract

Cervical intraepithelial neoplasia grade 2 (CIN 2) is an equivocal diagnosis with high interobserver variation. Owing to high regression rates of 50%, many countries recommend active surveillance of CIN 2, especially in women younger than age 25-30 years, where regression rates are even higher (ie, 60%). Additionally, excisional treatment is associated with increased risk of reproductive harm, particularly preterm birth. Active surveillance typically consists of semi-annual follow-up visits for up to 2 years, including colposcopy and either cytology, testing for human papillomavirus, or both. Excisional treatment is recommended for progression or persistent disease after 2 years. Because active surveillance in younger women is relatively new, knowledge on subsequent risk of cervical cancer is limited. Considering human papillomavirus latency, women undergoing active surveillance might be at higher risk of cervical cancer than women undergoing excisional treatment. Furthermore, there are

Active expectancy as alternative to treatment for cervical intraepithelial neoplasia grade 2 in women aged 25 to 30 years: ExCIN2—a prospective clinical multicenter cohort study

“…CIN2 has previously been the threshold for excisional treatment, but during the last decade, many countries have implemented active surveillance for women aged under 25 years with CIN2 owing to the high regression rate. 6 Local excision of the cervix, nowadays mostly performed by the loop electrosurgical excision procedure (LEEP), increases the risk of preterm birth and midtrimester pregnancy loss in women conceiving after treatment. 7e10 The trend of giving birth at older ages, wherein the risk of previous exposure to cervical treatment is increased, adds to this major problem.…”

High prevalence of HPV16 and high‐grade cytology in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2

“…In this study on women undergoing active surveillance for CIN2 in other countries such as Sweden, Norway or Australia due to variable criteria across countries. 1,[6][7][8] Thus, our findings emphasize the importance of more follow-up studies on various risk factors for CIN2 progression, including factors such as lesion size, type of transformation zone and/or patient consent, since some of these criteria have been applied in other countries such as in the US, UK and Finland. 1,[9][10][11] This may help understand criteria which may enable risk stratification; women with a high likelihood of regression who would benefit from active surveillance vs those with a low likelihood of regression who would benefit from immediate LLETZ.…”

“…1,[6][7][8] Thus, our findings emphasize the importance of more follow-up studies on various risk factors for CIN2 progression, including factors such as lesion size, type of transformation zone and/or patient consent, since some of these criteria have been applied in other countries such as in the US, UK and Finland. 1,[9][10][11] This may help understand criteria which may enable risk stratification; women with a high likelihood of regression who would benefit from active surveillance vs those with a low likelihood of regression who would benefit from immediate LLETZ. Finally, our study highlights a need to improve the diagnostic accuracy of the CIN2 diagnosis as 26.6% of CIN2 cases were classified as normal or low-grade upon expert review, suggesting a significant risk of overtreatment if all women with CIN2 are treated surgically.…”

“…Because active surveillance has only recently been implemented, not much is known on which criteria to use and, thus, criteria vary considerably between countries. 1,[6][7][8][9][10][11] In screening populations, a high-grade cytology result is associated with higher likelihood of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) as compared to a normal or low-grade cytology. 9 Consequently, active surveillance is not recommended in women with a high-grade cytology result in some countries such as Sweden or Australia.…”

Distinct mechanism of cervical cancer cell death caused by the investigational new drug SHetA2

“…Women diagnosed with cervical intraepithelial neoplasia 3 (CIN3) have significant risk of developing cervical cancer and the standard of care for these patients is to have their cervical lesions removed by a loop electrosurgical excision procedure (LEEP), large loop excision of the transformation zone (LLETZ) or cold-knife conization ( 33 ). Depending on the Country, women diagnosed with CIN 2 are triaged to either active surveillance or one of these surgical procedures ( 34 ). Many women who are triaged to active surveillance feel anxiety about their risk of developing cervical cancer ( 35 ).…”